Receptor-ligand interaction-based virtual screening for novel Eg5/kinesin spindle protein inhibitors.
J Med Chem
; 55(6): 2561-73, 2012 Mar 22.
Article
em En
| MEDLINE
| ID: mdl-22309208
ABSTRACT
Eg5/KSP is a promising mitotic spindle target for drug discovery in cancer chemotherapy and the development of agents against fungal diseases. A range of Eg5 targeting compounds identified by in vitro or cell-based screening is currently in development. We employed structure-based virtual screening of a database of 700, 000 compounds to identify three novel Eg5 inhibitors bearing quinazoline (24) or thioxoimidazolidine (30 and 37) scaffolds. The new compounds inhibit Eg5 ATPase activity, show growth inhibition in proliferation assays, and induce monoastral spindles in cells, the characteristic phenotype for Eg5 inhibiting agents. This is the first successful reported procedure for the identification of Eg5 inhibitors via receptor-ligand interaction-based virtual screening.
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1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
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Modelos Moleculares
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Bases de Dados Factuais
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Cinesinas
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Imidazolidinas
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Antineoplásicos
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article